ACE inhibitor + thiazide diuretic (fixed-dose) Pregnancy: Contraindicated in the second and third trimesters; ACE inhibitors are not recommended in the first trimester. Stop treatment immediately when pregnancy is diagnosed and start alternative therapy if appropriate. Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or pre-eclampsia, and should not be used for essential hypertension in pregnancy except in rare situations where no other treatment could be used. Breast-feeding: not recommended for preterm infants or for the first few weeks after delivery.

Enalapril with hydrochlorothiazide

Brand names: Innozide

This is a fixed-dose combination of the ACE inhibitor enalapril with the thiazide diuretic hydrochlorothiazide, used to treat hypertension in patients suitably controlled on the two components.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: One tablet (enalapril maleate 20 mg / hydrochlorothiazide 12.5 mg) daily

Route: Oral, with or without food

Frequency: Once daily

Source is the fixed-combination SPC 'Enalapril Maleate and Hydrochlorothiazide 20 mg/12.5 mg Tablets'; the recommended dosage is one tablet taken once daily. Individual dose titration with both active substances may be recommended. When clinically appropriate, direct change from ACE inhibitor monotherapy to the fixed combination may be considered. Sodium/volume depletion: the initial dose is 5 mg of enalapril or lower, with an individual and progressive introduction of enalapril and hydrochlorothiazide. Elderly: efficacy and tolerability were similar in elderly and younger hypertensive patients; in case of physiological renal impairment, titration with enalapril alone is recommended prior to using the fixed combination. Paediatric: safety and efficacy in children and adolescents aged under 18 have not been established. SPC §4.2 states no maximum dose for the fixed combination.

Dose adjustments

Renal

Creatinine clearance between 30 and 80 ml/min: the 20 mg/12.5 mg fixed combination should be used only after titration of the individual components; loop diuretics are preferred to thiazides in this population; keep the dose as low as possible and monitor potassium and creatinine periodically (e.g. every 2 months once treatment is stabilised). Creatinine clearance ≤30 ml/min: contraindicated (§4.3).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients
Severe renal impairment (creatinine clearance ≤30 ml/min)
Anuria
History of angioneurotic oedema associated with previous ACE-inhibitor therapy; hereditary or idiopathic angioedema
Concomitant use with sacubitril/valsartan — must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan
Hypersensitivity to sulfonamide-derived drugs
Second and third trimesters of pregnancy
Severe hepatic impairment
Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²)

Side effects

Very common: dizziness, blurred vision, cough, nausea
Common: headache, syncope, taste alteration, depression
Common: hypotension, orthostatic hypotension, rhythm disturbances, angina pectoris, tachycardia
Common: hypokalaemia, hyperuricaemia, increased cholesterol and triglycerides
Common: rash (exanthema); hypersensitivity/angioneurotic oedema of the face, extremities, lips, tongue, glottis
Rare: hepatic failure, hepatic necrosis (may be fatal), hepatitis, jaundice; neutropenia, thrombocytopenia, agranulocytosis

Interactions

Sacubitril/valsartan — concomitant use contraindicated; 36-hour gap required after the last sacubitril/valsartan dose (§4.3)
Aliskiren-containing products — contraindicated in diabetes mellitus or renal impairment (§4.3, §4.5)
Diuretic therapy, dietary salt restriction, diarrhoea or vomiting (volume depletion) — symptomatic hypotension more likely; determine serum electrolytes regularly (§4.4)
Combination of enalapril with a low-dose diuretic does not exclude the possibility of hyperkalaemia (§4.4)
Lithium — interaction flagged in SPC §4.4 (text truncated in the fetched extract; verify against the full SPC)
NOTE: SPC §4.5 was not captured in the fetched extract — clinician to review the full interactions section

Clinical monograph

How it works

Enalapril blocks angiotensin-converting enzyme to reduce angiotensin II and aldosterone, causing vasodilatation, while hydrochlorothiazide promotes renal sodium and water excretion; the combination gives complementary blood-pressure lowering and the ACE inhibitor offsets thiazide-induced potassium loss.

Prescribing in practice

Both components are contraindicated in pregnancy, and ACE inhibitors carry a risk of angioedema, so the combination must be avoided in women who are or may become pregnant.
The two drugs have opposing effects on potassium and the thiazide can disturb sodium, magnesium, urate and glucose, so electrolytes and renal function must be checked, particularly with concurrent renin-angiotensin or potassium-affecting drugs.
Risk of first-dose and volume-related hypotension and of acute kidney injury, especially in volume-depleted patients or those also taking NSAIDs (the "triple whammy").

Monitoring

Check renal function and electrolytes before starting and after initiation or dose change, alongside regular blood pressure review.

Counselling the patient

Stop the tablet and seek urgent help if you notice swelling of the face, lips, tongue or throat.
Tell us straight away if you become pregnant or are planning pregnancy.
A dry cough or dizziness on standing can occur; report persistent symptoms.

Evidence & guidelines

Fixed-dose ACE inhibitor with thiazide combinations are well established for hypertension where single-tablet therapy aids adherence.

Reference: NICE NG136; MHRA Drug Safety Update; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways